Coutts Group

Cancer cells are exposed to a range of intrinsic and extrinsic stressors, including for example, metabolic, therapeutic, hypoxia and mechanical. Cells adapt and respond to stress within a highly dynamic tumour environment. Stress responses and the underlying mechanisms play crucial roles in cancer cell survival and disease progression. Importantly, understanding how cancer cells integrate responses to promote cancer cell survival remains a key challenge in cancer biology. Ideally by disrupting mechanisms that cancer cells use to tolerate stress we could enhance therapeutic efficacy and overcome drug resistance.

During stress responses signalling pathways impact on process such as autophagy, cell cycle regulation, and nuclear activities to enable survival. Actin and actin regulated processes are increasingly recognised to play a significant role in cell survival and outcome by impacting on both cytoplasmic and nuclear activities. Our research focusses on understanding how these survival pathways link to disease progression as well as nuclear processes that influence gene expression during stress responses. We aim to identify and understand how cancer cells regulate cell fate during stress responses, in particular, how signalling pathways influence cell survival as well as the role of nuclear architecture. Some of our current interests include:

1. Integration of cytoplasmic with nuclear events during the stress response.

A main aspect of the group is to explore how a p53 transcription co-factor and actin nucleation promoting factor, JMY, links cytoskeletal and nuclear events during the stress response. Our research identified a role for JMY-mediated actin-nucleation in the regulation of autophagosome formation during metabolic stress. This promotes cell survival by cytoplasmic JMY. Additionally, during the DNA damage response JMY‘s nuclear localisation promotes p53-dependent gene expression and influences DNA repair. Future work aims to better understand signalling that impacts on JMY’s activity and localisation during stress responses.

2. Nuclear structure and nuclear actin.

A key current interest is how nuclear actin is regulated and how this influences outcome during stress responses. We are interested in how filamentous nuclear actin is controlled and how nuclear actin links to nuclear structure (e.g., paraspeckles, nucleolus) as well as nuclear function.

We also have ongoing collaborations to understand novel regulators of cancer cell survival in breast and pancreatic cancers.

Dr Coutts’ complete publication record can be found in her ORCiD record: https://orcid.org/0000-0002-5005-1864